Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis-dependent plasticity

• Published in: Journal of physiology, Paris Paris, 2005-04, Vol.564 (1), p.3-19
• Main Authors: Arnold, Fiona J. L., Hofmann, Frank, Bengtson, C. Peter, Wittmann, Malte, Vanhoutte, Peter, Bading, Hilmar
• Format: Article
• Language: English
• Subjects: Animals; Bicuculline - pharmacology; Cells, Cultured; Cognitive Sciences; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Hippocampus - drug effects; Hippocampus - physiology; Life Sciences; Microelectrodes; Models, Biological; Molecular and Genomic Physiology; Nerve Net - drug effects; Nerve Net - physiology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons and Cognition; Patch-Clamp Techniques - methods; Proteins - metabolism; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Time Factors; Transcription, Genetic - drug effects; Transcription, Genetic - physiology
• ISSN: 0022-3751; 0928-4257; 1469-7793
• DOI: 10.1113/jphysiol.2004.077446

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABA A receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor-mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal-regulated kinase (ERK)1/2 signalling and translation of pre-existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis-dependent form of plasticity. The non-invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long-term potentiation in brain slices) and facilitates the search for activity-regulated genes critical for late-phase plasticity.